Cold ischemia time in liver transplantation: An overview.

The standard approach to organ preservation in liver transplantation is by static cold storage and the time between the cross-clamping of a graft in a donor and its reperfusion in the recipient is defined as cold ischemia time (CIT). This simple definition reveals a multifactorial time frame that depends on donor hepatectomy time, transit time, and recipient surgery time, and is one of the most important donor-related risk factors which may influence the graft and recipient's survival. Recently, the growing demand for the use of marginal liver grafts has prompted scientific exploration to analyze ischemia time factors and develop different organ preservation strategies. This review details the CIT definition and analyzes its different factors. It also explores the most recent strategies developed to implement each timestamp of CIT and to protect the graft from ischemic injury.

Preoperative Super-Selective Embolization versus "On-Clamp" Laparoscopic Partial Nephrectomy for T1 Renal Tumors- A Prospective Randomized Study.

To analyze and compare the intraoperative and post-operative outcomes of "on-clamp" laparoscopic partial nephrectomy (LPN) with "preoperative super-selective angioembolization" before LPN. This randomized clinical study was conducted at Gauhati Medical College Hospital, Guwahati, India, between November 2021 and November 2023. Adult patients of either gender diagnosed with T1 renal tumors were included in the study. All patients underwent diethylenetriamine pentaacetate scan preoperatively and at 1-month follow-up. The patients were randomized using a parallel group design with an allocation ratio of 1:1 to receive either preoperative angioembolization followed by LPN or conventional "on-clamp" LPN. Demographic and baseline parameters were recorded along with pre- and post-operative data. There was no significant difference between the two groups in terms of age (P = 0.11), gender distribution (P = 0.32), body mass index (P = 0.43), preoperative hemoglobin (P = 0.34), and preoperative estimated glomerular filtration rate (eGFR; P = 0.64). One patient in the embolization group required radical nephrectomy because of accidental backflow of glue into the renal artery during embolization whereas four patients required clamping due to inadequate embolization. Preoperative super-selective embolization yielded significantly less blood loss, compared to "on-clamp" LPN (145 [50.76 mL] vs. 261 [66.12 mL], P < 0.01). There was no significant difference between post-operative eGFR (at 1 month) between the two groups (P = 0.71). Preoperative embolization offers improved outcomes in the dissection plane, total operative time, and blood loss, compared to conventional "on-clamp" LPN but has no significant effect on change in eGFR.

Erratum: Advantages and limitations of clinical scores for donation after circulatory death liver transplantation.

[This corrects the article DOI: 10.3389/fsurg.2021.808733.].

CD47 blockade reduces ischemia/reperfusion injury in murine heart transplantation and improves donor heart preservation.

BACKGROUND: Myocardial ischemia-reperfusion injury (MIRI) is an important cause of early dysfunction and exacerbation of immune rejection in transplanted hearts. The integrin-related protein CD47 exacerbates myocardial ischemia-reperfusion injury by inhibiting the nitric oxide signaling pathway through interaction with thrombospondin-1 (TSP-1). In addition, the preservation quality of the donor hearts is a key determinant of transplant success. Preservation duration beyond four hours is associated with primary graft dysfunction. We hypothesized that blocking the CD47-TSP-1 system would attenuate ischemia-reperfusion injury in the transplanted heart and, thus, improve the preservation of donor hearts. METHODS: We utilized a syngeneic mouse heart transplant model to assess the effect of CD47 monoclonal antibody (CD47mAb) to treat MIRI. Donor hearts were perfused with CD47mAb or an isotype-matched control immunoglobulin (IgG2a) and were implanted into the abdominal cavity of the recipients after being stored in histidine-tryptophan-ketoglutarate (HTK) solution at 4 °C for 4 h or 8 h. RESULTS: At both the 4-h and 8-h preservation time points, mice in the experimental group perfused with CD47mAb exhibited prolonged survival in the transplanted heart, reduced inflammatory response and oxidative stress, significantly decreased inflammatory cell infiltration, and fewer apoptosis-related biomarkers. CONCLUSION: The application of CD47mAb for the blocking of CD47 attenuates MIRI as well as improves the preservation and prognosis of the transplanted heart in a murine heart transplant model.

Characteristics of Delayed Graft Function and Long-Term Outcomes After Kidney Transplantation From Brain-Dead Donors: A Single-Center and Multicenter Registry-Based Retrospective Study.

Delayed graft function (DGF) after kidney transplantation is common and associated with worse graft outcomes. However, little is known about factors affecting graft survival post-DGF. We studied the association of cold ischemia time (CIT) and Kidney Donor Profile Index (KDPI) with the long-term outcomes of deceased brain-dead donor kidneys with and without DGF. Data from Finland (n = 2,637) and from the US Scientific Registry of Transplant Recipients (SRTR) registry (n = 61,405) was used. The association of KDPI and CIT with the graft survival of kidneys with or without DGF was studied using multivariable models. 849 (32%) kidneys had DGF in the Finnish cohort. DGF and KDPI were independent risk factors for graft loss, [HR 1.32 (95% CI 1.14-1.53), p < 0.001, and HR 1.01 per one point (95% CI 1.01-1.01), p < 0.001, respectively], but CIT was not, [HR 1.00 per CIT hour (95% CI 0.99-1.02), p = 0.84]. The association of DGF remained similar regardless of CIT and KDPI. The US cohort had similar results, but the association of DGF was stronger with higher KDPI. In conclusion, DGF and KDPI, but not CIT, are independently associated with graft survival. The association of DGF with worse graft survival is consistent across different CITs but stronger among marginal donors.

Resuscitative endovascular balloon occlusion of the aorta (REBOA) successfully used in interhospital transport.

Resuscitative endovascular balloon occlusion of the aorta (REBOA) is primarily utilized in traumatic noncompressible torso hemorrhage as a temporary approach to buying time until a definite intervention could be obtained. REBOA is mostly reported in inhospital or prehospital settings. Its interhospital transfer use remains controversial. In this report, we present a case with pelvic fracture and hemorrhagic shock who underwent REBOA placement and was transferred from a local hospital to a trauma center successfully for further surgical intervention.

Prevention of Delayed Graft Function in Kidney Transplant Recipients through a Continuous Infusion of the Prostaglandin Analogue Iloprost: A Single-Center Prospective Study.

BACKGROUND: Delayed graft function (DGF) is common after kidney transplantation from deceased donors and may significantly affect post-transplant outcomes. This study aimed to evaluate whether an innovative approach, based on the administration of the intravenous prostaglandin analogue iloprost, could be beneficial in reducing the incidence of DGF occurring after kidney transplantation from deceased donors. METHODS: This prospective, randomized (1:1), placebo-controlled study enrolled all consecutive patients who received a kidney transplant from a deceased donor from January 2000 to December 2012 and who were treated in the peri-transplant period with the prostaglandin analogue iloprost at 0.27 µg/min through an elastomeric pump (treatment group) or with a placebo (control group). RESULTS: A total of 476 patients were included: DGF was reported in 172 (36.1%) patients in the entire cohort. The multivariate analysis showed that the donor's age > 70 years (OR 2.50, 95% confidence interval (CI): 1.40-3.05, p < 0.001), cold ischemia time > 24 h (OR 2.60, 95% CI: 1.50-4.51, p < 0.001), the donor's acute kidney injury (OR 2.71, 95% CI: 1.61-4.52, p = 0.021) and, above all, the recipient's arterial hypotension (OR 5.06, 95% CI: 2.52-10.1, p < 0.0001) were the strongest risk factors for developing post-transplant DGF. The incidence of DGF was 21.4% in the treatment group and 50.9% in the control group (p < 0.001). Interestingly, among patients who developed DGF, those who received iloprost had a shorter duration of post-transplant DGF (10.5 ± 8.3 vs. 13.4 ± 6.7, days, p = 0.016). CONCLUSIONS: This study showed that the use of a continuous infusion of iloprost could safely and effectively reduce the incidence of DGF in recipients of deceased-donor kidneys, allowing a better graft functionality as well as a better graft survival.

Interaction between cold ischemia time and Kidney Donor Profile Index on postrenal transplant outcomes.

We analyzed whether there is an interaction between the Kidney Donor Profile Index (KDPI) and cold ischemia time (CIT) in recipients of deceased donor kidney transplant (KTs). Adults who underwent KTs in the United States between 2014 and 2020 were included and divided into 3 KDPI groups (≤20%, 21%-85%, >85%) and 4 CIT strata (<12, 12-17.9, 18-23.9, ≥24 hours). Multivariate analyses were used to test the interaction between KDPI and CIT for the following outcomes: primary graft nonfunction (PGNF), delayed graft function (DGF), estimated glomerular filtration rate (eGFR) at 6 and 12 months, patient survival, graft survival, and death-censored graft survival (DCGS). A total of 69,490 recipients were analyzed: 18,241 (26.3%) received a graft with KDPI ≤20%, 46,953 (67.6%) with KDPI 21%-85%, and 4,296 (6.2%) with KDPI >85%. Increasing KDPI and CIT were associated with worse post-KT outcomes. Contrary to our hypothesis, howerver, the interaction between KDPI and CIT was statistically significant only for PGNF and DGF and eGFR at 6 months. Paradoxically, the negative coefficient of the interaction suggested that increasing duration of CIT was more detrimental for low and intermediate-KDPI organs relative to high-KDPI grafts. Conversely, for mortality, graft survival, and DCGS, we found that the interaction between CIT and KDPI was not statistically significant. We conclude that, high KDPI and prolonged CIT are independent risk factors for inferior outcomes after KT. Their interaction, however, is statistically significant only for the short-term outcomes and more pronounced on low and intermediate-KDPI grafts than high-KDPI kidneys.

Re-assessing prolonged cold ischemia time in kidney transplantation through machine learning consensus clustering.

BACKGROUND: We aimed to cluster deceased donor kidney transplant recipients with prolonged cold ischemia time (CIT) using an unsupervised machine learning approach. METHODS: We performed consensus cluster analysis on 11 615 deceased donor kidney transplant patients with CIT exceeding 24 h using OPTN/UNOS data from 2015 to 2019. Cluster characteristics of clinical significance were identified, and post-transplant outcomes were compared. RESULTS: Consensus cluster analysis identified two clinically distinct clusters. Cluster 1 was characterized by young, non-diabetic patients who received kidney transplants from young, non-hypertensive, non-ECD deceased donors with lower KDPI scores. In contrast, the patients in cluster 2 were older and more likely to have diabetes. Cluster 2 recipients were more likely to receive transplants from older donors with a higher KDPI. There was lower use of machine perfusion in Cluster 1 and incrementally longer CIT in Cluster 2. Cluster 2 had a higher incidence of delayed graft function (42% vs. 29%), and lower 1-year patient (95% vs. 98%) and death-censored (95% vs. 97%) graft survival compared to Cluster 1. CONCLUSIONS: Unsupervised machine learning characterized deceased donor kidney transplant recipients with prolonged CIT into two clusters with differing outcomes. Although Cluster 1 had more favorable recipient and donor characteristics and better survival, the outcomes observed in Cluster 2 were also satisfactory. Overall, both clusters demonstrated good survival suggesting opportunities for transplant centers to incrementally increase CIT.

Robot-assisted Partial Nephrectomy Using Intra-arterial Renal Hypothermia for Highly Complex Endophytic or Hilar Tumors: Case Series and Description of Surgical Technique.

Background: In partial nephrectomy for highly complex tumors with expected long ischemia time, renal hypothermia can be used to minimize ischemic parenchymal damage. Objective: To describe our case series, surgical technique, and early outcomes for robot-assisted partial nephrectomy (RAPN) using intra-arterial cold perfusion through arteriotomy. Design setting and participants: A retrospective analysis was conducted of ten patients with renal tumors (PADUA score 9-13) undergoing RAPN between March 2020 and March 2023 with intra-arterial cooling because of expected arterial clamping times longer than 25 min. Surgical procedure: Multiport transperitoneal RAPN with full renal mobilization and arterial, venous, and ureteral clamping was performed. After arteriotomy and venotomy, 4°C heparinized saline is administered intravascular through a Fogarty catheter to maintain renal hypothermia while performing RAPN. Measurements: Demographic data, renal function, console and ischemia times, surgical margin status, hospital stay, estimated blood loss, and complications were analyzed. Results and limitations: The median warm and cold ischemia times were 4 min (interquartile range [IQR] 3-7 min) and 60 min (IQR 33-75 min), respectively. The median rewarming ischemia time was 10.5 min (IQR 6.5-23.75 min). The median pre- and postoperative estimated glomerular filtration rate values at least 1 mo after surgery were 90 ml/min (IQR 78.35-90 ml/min) and 86.9 ml/min (IQR 62.08-90 ml/min), respectively. Limitations include small cohort size and short median follow-up (13 [IQR 9.1-32.4] mo). Conclusions: We demonstrate the feasibility and first case series for RAPN using intra-arterial renal hypothermia through arteriotomy. This approach broadens the scope for minimal invasive nephron-sparing surgery in highly complex renal masses. Patient summary: We demonstrate a minimally invasive surgical technique that reduces kidney infarction during complex kidney tumor removal where surrounding healthy kidney tissue is spared. The technique entails arterial cold fluid irrigation, which temporarily decreases renal metabolism and allows more kidneys to be salvaged.

The Association of Ischemia Type and Duration with Acute Kidney Injury after Robot-Assisted Partial Nephrectomy.

BACKGROUND: Acute kidney injury (AKI) after robot-assisted partial nephrectomy (RAPN) is a robust surrogate for chronic kidney disease. The objective of this study was to evaluate the association of ischemia type and duration during RAPN with postoperative AKI. MATERIALS AND METHODS: We reviewed all patients who underwent RAPN at our institution since 2011. The ischemia types were warm ischemia (WI), selective artery clamping (SAC), and zero ischemia (ZI). AKI was defined according to the Risk Injury Failure Loss End-Stage (RIFLE) criteria. We calculated ischemia time thresholds for WI and SAC using the Youden and Liu indices. Logistic regression and decision curve analyses were assessed to examine the association with AKI. RESULTS: Overall, 154 patients met the inclusion criteria. Among all RAPNs, 90 (58.4%), 43 (28.0%), and 21 (13.6%) were performed with WI, SAC, and ZI, respectively. Thirty-three (21.4%) patients experienced postoperative AKI. We extrapolated ischemia time thresholds of 17 min for WI and 29 min for SAC associated with the occurrence of postoperative AKI. Multivariable logistic regression analyses revealed that WIT ≤ 17 min (odds ratio [OR] 0.1, p < 0.001), SAC ≤ 29 min (OR 0.12, p = 0.002), and ZI (OR 0.1, p = 0.035) significantly reduced the risk of postoperative AKI. CONCLUSIONS: Our results confirm the commonly accepted 20 min threshold for WI time, suggest less than 30 min ischemia time when using SAC, and support a ZI approach if safely performable to reduce the risk of postoperative AKI. Selecting an appropriate ischemia type for patients undergoing RAPN can improve short- and long-term functional kidney outcomes.

Laparoscopic aspirator bracket: a new instrument facilitating the aspiration and exposure of operative field simultaneously in laparoscopic nephron-sparing surgery.

Background: This study aims to describe a novel laparoscopic aspirator bracket (LAB) and its use in laparoscopic nephron-sparing surgery (NSS) by a simple enucleation (SE) technique. Methods: A total of 123 renal tumor cases who underwent laparoscopic NSS via LAB or laparoscopic aspirator between July 2017 and April 2021 were retrospectively analyzed. General characteristics, perioperative data and postoperative follow-up data of patients were compared. Results: The application of LAB in laparoscopic renal tumor SE surgery shortened the operation time (88.58 ± 38.25 vs. 102.25 ± 35.84 min, p < 0.05) and improved the zero ischemia rate (18.75% vs. 3.39%, p < 0.05), shortened warm ischemia time (16.17 ± 5.16 vs. 19.39 ± 5.62 min, p < 0.05) and decreased intraoperative blood loss (166.19 ± 111.60 vs. 209.15 ± 127.10 ml, p < 0.05). In addition, the serum creatinine and eGFR values in the LAB group also showed faster and better renal function recovery. Conclusion: The new LAB could aspirate and expose the operative field with a single instrument. In operations that need to expose and aspirate simultaneously, such as in renal tumor simple enucleation, it could shorten operation time, reduce intraoperative blood loss and improve the postoperative renal function recovery.

Does tumor rupture during robot-assisted partial nephrectomy have an impact on mid-term tumor recurrences?

BACKGROUND: Intraoperative kidney tumor rupture (TR) can occur during robot-assisted partial nephrectomy (RAPN) in daily clinical practice, but there are no solid guidelines on the management and implications of it. The purpose of the study was to investigate the impact of TR on tumor recurrences, what a surgeon should do if this adverse event occurs, and how to avoid it. PATIENTS AND METHODS: We retrospectively analyzed the first 100 patients who underwent RAPN at University Medical Centre Ljubljana, between 2018 and 2021. Patients were stratified into 2 groups (TR and no-TR) and were compared according to patient, tumor, pathologic, perioperative and postoperative characteristics and tumor recurrences, using the Mann-Whitney U test and chi-squared test. RESULTS: Of the 100 patients, 14 had TR (14%); this occurred in tumors with higher RENAL nephrometry scores (P = 0.028) and mostly with papillary renal cell carcinomas (P = 0.043). Median warm ischemia time was longer for the TR group (22 vs. 15 min, P = 0.026). In terms of studied outcomes, there were no cases of local or distant recurrence after a median observation time of 39 months (interquartile range, 31-47 months) in both groups. We observed positive surgical margins on the final oncologic report in one case in the no-TR group. CONCLUSIONS: Tumor rupture during RAPN seems to be of no mid-term oncologic importance. According to presented results, we would recommend surgeons to proceed with tumor resection if this event occurs and abstain from conversion to radical nephrectomy or open partial nephrectomy. However, more similar cases should be studied to make more solid conclusions.

Time-Dependent Changes of Klotho and FGF-23 Levels after Kidney Transplantation: Role of Cold Ischemia Time, Renal Function and Graft Inflammation.

We investigated the evolution of serum klotho (s-Kl) and FGF-23 during the first two years post-kidney transplantation (KT), considering the cold ischemia time (CIT), glomerular filtration rate (GFR) and graft subclinical inflammation (SCI). We undertook a prospective, cohort, multicenter study of consecutive patients between April 2018 and January 2021 (with follow-up at 24 months). Subgroups were analyzed according to the median CIT (<14 vs. ≥14 h), the median GFR (≤40 vs. >40 mL/min/1.73 m2) and the presence of SCI at month 3. A total of 147 patients were included. s-Kl and fibroblast growth factor-23 (FGF-23) levels were measured at baseline and at months 3, 12 and 24. Graft biopsies (n = 96) were performed at month 3. All patients had low s-Kl levels at month 3. Patients with CIT < 14 h exhibited a significant increase in s-Kl at month 24. In patients with CIT ≥ 14 h, s-Kl at month 3 fell and lower s-Kl levels were seen at month 24. Patients with a GFR > 40 had a lesser decrease in s-Kl at month 3. FGF-23 fell significantly at months 3 and 12 in both GFR groups, a reduction maintained during follow-up. There were significant inter-group differences in s-Kl from months 3 to 24. CIT, GFR at 3 months and SCI were significantly associated with s-KI at month 3. A reduction in s-Kl at month 3 post-KT could be explained by longer CIT and delayed graft function as well as by impaired graft function. Early SCI may regulate s-Kl increase post-KT.

Stratified Analysis of Survival Benefit for ABO-incompatible Deceased-donor Liver Transplantation: Multicenter Propensity Score-matched Study.

Background and Aims: Liver transplantation (LT) using ABO-incompatible (ABOi) grafts can extend the donor pool to a certain extent and hence reduce the waiting time for transplantation. However, concerns of the impending prognosis associated with this option, especially for patients with liver failure and higher model for end-stage liver disease (MELD) scores, who tend to be more fragile during the waiting period before LT. Methods: Recipients undergoing LT for acute-on-chronic liver failure or acute liver failure were retrospectively enrolled at four institutions. Overall survival was compared and a Cox regression analysis was performed. Propensity score matching was performed for further comparison. Patients were stratified by MELD score and cold ischemia time (CIT) to determine the subgroups with survival benefits. Results: Two hundred ten recipients who underwent ABOi LT and 1,829 who underwent ABO compatible (ABOc) LT were enrolled. The 5-year overall survival rate was significantly inferior in the ABOi group compared with the ABOc group after matching (50.6% vs. 75.7%, p<0.05). For patients with MELD scores ≤30, using ABOi grafts achieved a comparable overall survival rate as using ABOc grafts (p>0.05). Comparison of the survival rates revealed no statistically significant difference for patients with MELD scores ≥40 (p>0.05). For patients with MELD scores of 31-39, the overall survival rate was significantly inferior in the ABOi group compared with the ABOc group (p<0.001); however, the rate was increased when the liver graft CIT was<8 h. Conclusions: For recipients with MELD scores ≤30, ABOi LT had a prognosis comparable to that of ABOc LT and can be regarded as a feasible option. For recipients with MELD scores ≥40, ABOi should be adopted with caution in emergency cases. For recipients with MELD scores of 31-39, the ABOi LT prognosis was worse. However, those patients benefited from receiving ABOi grafts with a CIT of <8 h.

Cinnamaldehyde protects donor heart from cold ischemia-reperfusion injury via the PI3K/AKT/mTOR pathway.

With the growing shortage of organs, improvements in donor organ protection are needed to meet the increasing demands for transplantation. Here, the aim was to investigate the protective effect of cinnamaldehyde against ischemia-reperfusion injury (IRI) in donor hearts exposed to prolonged cold ischemia. Donor hearts were harvested from rats pretreated with or without cinnamaldehyde, then subjected to 24 h of cold preservation and 1 h of ex vivo perfusion. Hemodynamic changes, myocardial inflammation, oxidative stress, and myocardial apoptosis were evaluated. The PI3K/AKT/mTOR pathway involved in the cardioprotective effects of cinnamaldehyde was explored through RNA sequencing and western blot analysis. Intriguingly, cinnamaldehyde pretreatment remarkably improved cardiac function through increasing coronary flow, left ventricular systolic pressure, +dp/dtmax, and -dp/dtmax, decreasing coronary vascular resistance and left ventricular end-diastolic pressure. Moreover, our findings indicated that cinnamaldehyde pretreatment protected the heart from IRI by alleviating myocardial inflammation, attenuating oxidative stress, and reducing myocardial apoptosis. Further studies showed that the PI3K/AKT/mTOR pathway was activated after cinnamaldehyde treatment during IRI. The protective effects of cinnamaldehyde were abolished by LY294002. In conclusion, cinnamaldehyde pretreatment alleviated IRI in donor hearts suffering from prolonged cold ischemia. Cinnamaldehyde exerted cardioprotective effects through the activation of the PI3K/AKT/mTOR pathway.

Risk of prolonged ischemic time linked to use of cardiopulmonary bypass during implantation for lung transplantation in the United Kingdom.

BACKGROUND: Some degree of ischemia is inevitable in organ transplantation, and for most, if not all organs, there is a relationship between ischemic time and transplant outcome. The contribution of ischemic time to lung injury is unclear, with conflicting recent data. In this study, we investigate the impact of ischemia time on survival after lung transplantation in a large national cohort. METHODS: We studied the outcomes for 1,565 UK adult lung transplants over a 12-year period, for whom donor, transplant, and recipient data were available from the UK Transplant Registry. We examined the effect of ischemia time (defined as donor cross-clamp to recipient reperfusion) and whether standard cardiopulmonary bypass was used using Cox proportional hazards models, adjusting for other risk factors. RESULTS: The total ischemic time increased from a median under 5 hours in 2003 to over 6.2 hours in 2013. Our findings show that, when the cardiopulmonary bypass was used, there was an increase in the hazard of death (of 13% [95% CI: 5%-21%] for 1-year patient survival) for each hour of total ischemic time. However, if the cardiopulmonary bypass was not used for implantation, this link disappeared-there was no statistically significant change in mortality with increasing ischemic time. CONCLUSIONS: We document that avoidance of bypass may remove ischemic time, within the limits of our observed range of ischemic times, as a risk factor for poor outcomes. Our data add to the evidence that bypass may be harmful to the donor lung.

Limited non-linear impact of warm ischemia time on renal functional decline after partial nephrectomy: a propensity score-matched study.

OBJECTIVE: To quantificationally illustrate the impact of ischemia time (IT) on renal function decline after partial nephrectomy (PN), especially for patients with compromised baseline renal function (estimated glomerular filtration rate [eGFR] < 90 mL/min/1.73 m2). METHODS: Patients undergoing PN during 2014-2021 from a prospectively maintained database were reviewed. Propensity score matching (PSM) was employed to balance the possible covariates between patients with or without baseline compromised renal function. Specifically, the relationship of IT with postoperative renal function was illustrated. Two machine learning methods (logistic least absolute shrinkage and selection operator [LASSO] logistic regression and random forest) were applied to quantify the relative impact of each covariables. RESULTS: The average drop percent of eGFR was -10.9% (- 12.2%, - 9.0%). Multivariable Cox proportional regression and linear regression analyses identified five risk factors for renal function decline, namely RENAL Nephrometry Score (RNS), age, baseline eGFR, diabetes and IT (all p < 0.05). Specifically, the relationship of IT with postoperative functional decline emerged as non-linear, with an increase from 10-30 min and a plateau afterwards among patients with normal function (eGFR ≥ 90 mL/min/1.73 m2), whereas with an increase from 10 to 20 min and a plateau afterwards among patients with compromised function (eGFR < 90 mL/min/1.73 m2). Furthermore, the coefficient's path and random forest analysis revealed that the top two most important features were RNS and age. CONCLUSION: IT exhibits the secondarily non-linear relationship with postoperative renal function decline. Patients with compromised baseline renal function are less tolerant to ischemia damage. The use of a single cut-off interval of IT in the setting of PN is flawed.

The role of warm ischemia time on functional outcomes after robotic partial nephrectomy: a radionuclide renal scan study from the clock randomized trial.

PURPOSE: To evaluate the relationship between warm ischemia time (WIT) duration and renal function after robot-assisted partial nephrectomy (RAPN). METHODS: The CLOCK trial is a phase 3 randomized controlled trial comparing on- vs off-clamp RAPN. All patients underwent pre- and postoperative renal scintigraphy. Six-month absolute variation of eGFR (AV-GFR), rate of relative variation in eGFR over 25% (RV-GFR > 25), absolute variation of split renal function (SRF) at scintigraphy (AV-SRF). The relationships WIT/outcomes were assessed by correlation graphs and then modeled by uni- and multivariable regression. RESULTS: 324 patients were included (206 on-clamp, 118 off-clamp RAPN). Correlation graphs showed a threshold on WIT equal to 10 min. The differences in outcome measures between cases with WIT < vs ≥ 10 min were: AV-GFR - 3.7 vs - 7.5 ml/min (p < 0.001); AV-SRF - 1% vs - 3.6% (p < 0.001); RV-GFR > 25 9.3% vs 17.8% (p = 0.008). Multivariable models found that AV-GFR was related to WIT ≥ 10 min (regression coefficient [RC] - 0.52, p = 0.019), age (RC - 0.35, p = 0.001) and baseline eGFR (RC - 0.30, p < 0.001); RV-GFR > 25 to WIT ≥ 10 min (odds ratio [OR] 1.11, p = 0.007) and acute kidney injury defined as > 50% increase in serum creatinine (OR 19.7, p = 0.009); AV-SRF to WIT ≥ 10 min (RC - 0.30, p = 0.018), baseline SRF (RC - 0.76, p < 0.001) and RENAL score (RC - 0.60. p = 0.028). The main limitation was that the CLOCK trial was designed on a different endpoint and therefore the present analysis could be underpowered. CONCLUSIONS: Up to 10 min WIT had no consequences on functional outcomes. Above the 10-min threshold, a statistically significant, but clinically negligible impact was found.

Identification of predictive factors for outcomes after robot-assisted partial nephrectomy based on three-dimensional reconstruction of preoperative enhanced computerized tomography.

Background: Information from the RENAL score is limited. This study aimed to identify new parameters based on three-dimensional (3D) reconstruction of preoperative enhanced computerized tomography (CT) for predicting outcomes after robot-assisted partial nephrectomy (RPN). Materials and methods: The records of kidney cancer patients who underwent RPN at Tongji Hospital from March 2015 to July 2019 were reviewed. Demographic data, laboratory examinations, postoperative hospitalization time, and enhanced CT were retrospectively collected. Some tumor parameters were obtained from 3D reconstruction of CT data. The association between these predictive factors and outcomes after RPN was analyzed. Results: A larger tumor bed area (TBA) was associated with a longer warm ischemia time (WIT) (P-value <0.001) and tumor resection time (P-value <0.001). Moreover, TBA was significantly associated with the elevation of postoperative creatinine (P-value = 0.005). TBA (P = 0.008), distance from the tumor to the first bifurcation of the renal artery (DTA) (P <0.034), and RENAL score (P = 0.005) were significantly associated with WIT in univariate logistic regression. In multivariate logistic regression, TBA (P = 0.026) and DTA (P = 0.048) were independent risk factors for prolonged WIT (over 25 min). The predictive effect of the combination of TBA, DTA, and RENAL score was higher than the predictive effect of RENAL score alone for WIT (area under curve: 0.786 versus 0.72). Conclusion: TBA and DTA are independently associated with the WIT of RPN, which provides additional assessment value for the complexity of kidney cancer in RPN over the RENAL score.